Phenolic groups occur ubiquitously in many natural products and also form an important functional group in synthetic organic chemicals. Often times, it is necessary to perform reactions on these molecules containing the phenolic group function. Phenolic —OH groups activate the reactivity of aromatic nucleus towards electrophilic substitution so heavily that selectivity of the reactions is lost many a time. Also, the acidity of the phenolic hydrogens prevents performance of acid-sensitive reactions such as carbanion formation. Hence often times it is necessary to protect the phenolic functions, namely the phenolic —OH group suitably. Benzyl groups have been used extensively for the protection of phenolic groups (Wuts, P G M, Greene's Protective Groups in Organic Synthesis, 4th edition, John Wiley & Sons, 2007, pages 396-406), their (benzyl group) removal has always been effected by catalytic hydrogenation. The use of catalytic hydrogenation a priori cannot be performed if the molecule contains unsaturation such as carbon-carbon multiple bonds that may get hydrogenated simultaneously. Use of t-butyl groups has been considered. But the installation as well as the removal of t-butyl groups from phenolic substrates is always not very convenient (Wuts, P G M, Greene's Protective Groups in Organic Synthesis, 4th edition, John Wiley & Sons, 2007, page 396). While installation of t-butyl groups requires isobutylene or an unstable t-butyl halide, their (t-butyl group) removal to release phenolic groups often requires highly acidic conditions. Tetrahydropyranyl (THP) ethers is another choice. However protection of phenolic groups as THP ethers and their subsequent use is a studious operation and introduces additional elements of chirality. This results in, if multiple phenolic groups are present in the substrate, several diasteromers of the product, often complicating analysis and isolation issues. Protection of phenolic groups with acyl moiety is another strategy. However this also is also limited by the liability of acyl groups even in mildly basic conditions.
Phenolic groups can be protected as alkyl ethers. Foremost among them are methyl ethers (Wuts, P G M, Greene's Protective Groups in Organic Synthesis, 4th edition, John Wiley & Sons, 2007, pages 370-382). Introduction of methyl group onto a phenolic moiety is simple. Common reagents such as methyl iodide, dimethyl sulfate, diazomethane or more recently environmentally acceptable dimethyl carbonate (Perosa, A; Selva, M; Tundo, P & Zordan, F; 2000, Synlett., 272) can be judiciously used to convert phenolic groups to the corresponding methyl ethers. Conversion to other ethers such as ethyl ethers also follows a similar strategy.
Once the phenolic group is protected as an ether, reactions could be performed on the molecule; Finally the ether must be deprotected to release the parent phenol. Several methods have been described in prior art. They suffer from one disadvantage or another.
We describe in this invention an unique method of O-dealkylation